The role of phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase signaling pathway in diazoxide-postconditioning against myocardial ischemia/reperfusion injury in rats

Abstract

Objective To study the role of phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in diazoxide-postconditioning against in vivo rat myocardial ischemia/reperfusion (I/R) injury.Methods Forty SD rats were randomly divided into five groups:sham operation group (S),I/R,diazoxide group (D),inhibitor of PI3K wortmannin group (W) and diazoxide + wortmannin group (DW).In vivo myocardial I/R injury model was made by ligation of left anterior descending coronary artery 30 min followed by 120 min reperfusion except for S group.Each group was infused respectively with 0.1％ dimethyl sulfoxide (DMSO),0.1％ DMSO,diazoxide 7 mg/kg,wortmannin 15 μg/kg and diazoxide via the femoral vein 5 min before reperfusion,and wortmannin was given 5 min before administration of diazoxide in DW group.All drugs were continuously infused for 15 min.At the end of reperfusion,the plasma concentration of cardiac troponin Ⅰ (cTnI) was measured; myocardial pathological changes were examined by HE staining; and the expression of eNOS was evaluated via immunohistochemisty.Results Compared with S group,concentration of cTnI was significantly decreased (P＜0.01),myocardium damaged obviously,and the expression of eNOS was markedly increased in other four groups.Compared with I/R group,concentration of cTnI was significantly decreased [(36.5±5.2) μg/L and (44.5±4.5) μg/L vs (64.7±11.1) μg/L](P＜0.01) and myocardial pathological changes were markedly slighter,accompanying with significant high expression of eNOS [(0.515±0.136)％ Key words: Myocardial reperfusion injury; Diazoxide; 1-Phosphatidylinositol 3-kinase; Protein serine threonine kinase; Endothelial nitric oxide synthase